Names & Taxonomy

Uniprot ID:
P02788
Entry Name:
TRFL_HUMAN
Status:
reviewed
Protein Names:
Lactotransferrin (Lactoferrin) (EC 3.4.21.-) (Growth-inhibiting protein 12) (Talalactoferrin) [Cleaved into: Lactoferricin-H (Lfcin-H); Kaliocin-1; Lactoferroxin-A; Lactoferroxin-B; Lactoferroxin-C]
Gene Names:
LTF GIG12 LF
Gene Names Primary:
LTF
Organism:
Homo sapiens (Human)

Structure

Length:
710
Sequence:
MKLVFLVLLFLGALGLCLAGRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAARRARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Isoform 1: Secreted. Cytoplasmic granule. Note=Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.; Isoform DeltaLf: Cytoplasm. Nucleus. Note=Mainly localized in the cytoplasm.

Function

Function:
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.; Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity, which depends on the extracellular cation concentration. Antimicrobial properties include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane. Can also prevent bacterial biofilm development in P.aeruginosa infection. Has weak antifungal activity against C.albicans. Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection. Can inhibit papillomavirus infections. Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with the lipopolysaccharide (LPS)-stimulated TLR4 signaling. Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells. Stimulates VEGFA-mediated endothelial cell migration and proliferation. Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs). Also binds specifically to pneumococcal surface protein A (pspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA.; Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection. N-terminal region shows strong antifungal activity against C.albicans. Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site.; Kaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes.; Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.; The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity.; Isoform DeltaLf: transcription factor with antiproliferative properties and ability to induce cell cycle arrest. Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.
Catalytic Activity:
Preferential at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin.
Active Site:
ACT_SITE 92 92
Cross Reference Drug Bank:
DB04743 DB08439
Gene Ontology Go:
cell surface
cytoplasm
extracellular exosome
extracellular region
extracellular space
nucleus
phagocytic vesicle lumen
protein complex
secretory granule
specific granule
DNA binding
heparin binding
iron ion binding
protein serine/threonine kinase activator activity
serine-type endopeptidase activity
antibacterial humoral response
antifungal humoral response
bone morphogenesis
cell redox homeostasis
cellular protein metabolic process
humoral immune response
innate immune response in mucosa
interaction with host
ion transport
iron assimilation by chelation and transport
negative regulation by host of viral process
negative regulation of apoptotic process
negative regulation of ATPase activity
negative regulation of lipopolysaccharide-mediated signaling pathway
negative regulation of osteoclast development
negative regulation of single-species biofilm formation in or on host organism
negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
negative regulation of viral genome replication
negative regulation of viral process
ossification
positive regulation of bone mineralization involved in bone maturation
positive regulation of chondrocyte proliferation
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of osteoblast differentiation
positive regulation of osteoblast proliferation
positive regulation of protein serine/threonine kinase activity
positive regulation of toll-like receptor 4 signaling pathway
regulation of cytokine production
regulation of tumor necrosis factor production
response to host immune response
retina homeostasis
transcription, DNA-templated
Gene Ontology Biological Process:
antibacterial humoral response
antifungal humoral response
bone morphogenesis
cell redox homeostasis
cellular protein metabolic process
humoral immune response
innate immune response in mucosa
interaction with host
ion transport
iron assimilation by chelation and transport
negative regulation by host of viral process
negative regulation of apoptotic process
negative regulation of ATPase activity
negative regulation of lipopolysaccharide-mediated signaling pathway
negative regulation of osteoclast development
negative regulation of single-species biofilm formation in or on host organism
negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
negative regulation of viral genome replication
negative regulation of viral process
ossification
positive regulation of bone mineralization involved in bone maturation
positive regulation of chondrocyte proliferation
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of osteoblast differentiation
positive regulation of osteoblast proliferation
positive regulation of protein serine/threonine kinase activity
positive regulation of toll-like receptor 4 signaling pathway
regulation of cytokine production
regulation of tumor necrosis factor production
response to host immune response
retina homeostasis
transcription, DNA-templated
Gene Ontology Molecular Function:
DNA binding
heparin binding
iron ion binding
protein serine/threonine kinase activator activity
serine-type endopeptidase activity
Gene Ontology Cellular Component:
cell surface
cytoplasm
extracellular exosome
extracellular region
extracellular space
nucleus
phagocytic vesicle lumen
protein complex
secretory granule
specific granule
Keywords:
3D-structure
Alternative promoter usage
Antibiotic
Antimicrobial
Complete proteome
Cytoplasm
DNA-binding
Direct protein sequencing
Disulfide bond
Glycoprotein
Heparin-binding
Hydrolase
Immunity
Ion transport
Iron
Iron transport
Metal-binding
Nucleus
Osteogenesis
Phosphoprotein
Polymorphism
Protease
Reference proteome
Repeat
Secreted
Serine protease
Signal
Transcription
Transcription regulation
Transport
Ubl conjugation
Interacts With:
P27958; P62157

Publication

PubMed ID:
2402455 9122171 11702692 22900286 14573629 14702039 16641997 15489334 1480183 2374734 6510420 6794640 1599934 8089135 8551695 16048952 25946035 3477300 7049727 6802759 2981589 3169987 1369293 9359845 11083624 10792619 11179314 12037568 12565886 12693969 12535064 15222485 15166119 16842782 17481742 17567961 17079302 18780401 19033648 19159218 20345905 20404350 21269460 22320386 24275569 2585506 1772635 1581307 8371268 15299444 8069634 15299793 8703903 8931543 8594202 9003186 10089508 10089347 10828980 11128996 12037297 12450380 15687491 16201406 17263370 17543335 9873069 22406253